A Randomized Clinical Trial Comparing the Effects of Antitussive Agents on Respiratory Center Output in Patients With Chronic Cough

Background Cough is produced by the same neuronal pool implicated in respiratory rhythm generation, and antitussive drugs acting at the central level, such as opioids, may depress ventilation. Levodropropizine is classified as a nonopioid peripherally acting antitussive drug that acts at the level of airway sensory nerves. However, the lack of a central action by levodropropizine remains to be fully established. We set out to compare the effects of levodropropizine and the opioid antitussive agent dihydrocodeine on the respiratory responses to a conventional CO 2 rebreathing test in patients with chronic cough of any origin. Methods Twenty-four outpatients (aged 39-70 years) with chronic cough were studied. On separate runs, each patient was randomly administered 60 mg levodropropizine, 15 mg dihydrocodeine, or a matching placebo. Subsequently, patients breathed a mixture of 93% oxygen and 7% CO 2 for 5 min. Fractional end-tidal CO 2 (Fetco 2 ) and inspiratory minute ventilation ( V ˙ i) were continuously monitored. Changes in breathing pattern variables were also assessed. Results At variance with dihydrocodeine, levodropropizine and placebo did not affect respiratory responses to hypercapnia ( P Conclusions The results are consistent with a peripheral action by levodropropizine; the assessment of ventilatory responses to CO 2 may represent a useful tool to investigate the central respiratory effects of antitussive agents. Trial Registry European Union Clinical Trials Register (EudraCT No.: 2013-004735-68); URL: https://www.clinicaltrialsregister.eu/